Behavioral parameters evaluation after homeopathic Zincum metallicum treatment: a transgenerational study in mice

Background: ZINCUM METALLICUM (ZM) is a homeopathic medicine whose materia medica is defined by diverse behavioral and mental symptoms, including depression. Moreover, as a microelement, zinc itself is involved in several functions of Central Nervous System, including development and cell maturity during the intra-uterus life. Aims: Herein, the putative transgenerational effects of different homeopathic potencies of ZM upon behavioral parameters in P and F1 generations were evaluated. Methodology: Since mice and the tail suspension test (TST) are references for evaluating antidepressant agent activity, the TST together with the open field test (OPT) and the elevated plus maze test (EPM) were used to analyze offspring behavioral parameters. All animal procedures were in agreement with the Brazilian ethical research practices and were approved by the institutional ethical committee (CEUA-UNIP) under the protocol 156/2013. Four groups of seven females Balb/C mice were exposed to 0,1mL of ZM 5cH, 30cH, 200cH and lactose 5cH, diluted in 250mL of drinking water, during pregnancy and post partum period, in a total of 31 days. The flasks were coded before the remedies administration and all experimental procedures, including statistical analysis were done in blind. The parents were previously distributed in a Completely Randomized Design for the mates, according to the TST previous results. Mothers were re-evaluated for TST after weaning and mice of F1 generation were evaluated for TST, EPM and OPT when they reached two months old. According to the time of immobilization in TST, animals were classified as healthy (h), intermediate (i) and depressed (d) (< 116; 117-180 and >180 seconds of immobilization, respectively). Results: No significant changes were seen among the groups regarding to the number of newborns, sex proportions, TST, OPT and EPM behavioral parameters, besides the fact that the treatment with ZM 200cH was associated to the majority of healthy F1 mice (male: n=8: 7h+1i+0d; female: n=8: 8h+0i+0d), in relation to the number of delivery per group (Fisher test, p ≤ 0.01). Treatment with ZM 5cH, instead, produced reduced number of pups with no male mouse among F1 generation. We conclude that the treatment of pregnant females with ZM 200cH produced the best results in F1 generation regarding reproduction and behavioral parameters and the treatment with ZM 5cH reduced births in relation to control. The involved mechanisms have to be elucidated in the next steps of the study.

Linalool as a Therapeutic and Medicinal Tool in Depression Treatment: A Review

: Depression is a prevalent disease worldwide, limiting psychosocial functioning and the human quality of life. Linalool is the main constituent of some essential oils from aromatic plants, representing about 70% of these volatile concentrates. Evidence of the linalool activity on the central nervous system, mainly acting as an antidepressant agent, is increasingly abundant. This review aimed to extend the knowledge of linalool's antidepressant action mechanisms, which is fundamental for future research, intending to highlight this natural compound as a new antidepressant phytomedication. A critical analysis is proposed here with probable hypotheses of the synergic mechanisms that support the evidence of antidepressant effects of the linalool. The literature search has been conducted in databases for published scientific articles before December 2020, using relevant keywords. Several pieces of evidence point to the anticonvulsant, sedative, and anxiolytic actions. In addition to these activities, other studies have revealed that linalool acts on the monoaminergic and neuroendocrine systems, inflammatory process, oxidative stress, and neurotrophic factors, such as BDNF, wherein consist of the considerable advances in the knowledge of the etiology of depression. In this context, linalool emerges as a promising bioactive compound in the therapeutic arsenal, capable of interacting with numerous pathophysiological factors and acting on several targets. This review claims to contribute to future studies, highlighting the gaps in the linalool knowledge, as its kinetics, doses, routes of administration, and multiple targets of interaction, to clarify its antidepressant activity.

A Review on Analytical Method for Determination of Venlafaxine HCl in Bulk and Pharmaceutical dosage form

Venlafaxine HCl is one of the antidepressant agent which comes under the category of serotonin-norepinephrine reuptake inhibitor i.e SNRI. This medication is usually used to treat major depressive disorder in adult. It may help to improve the mood and energy level and also to regain the interest in daily activities in the depressed person. The present review focus on various approaches for the analysis on Venlafaxine in bulk and pharmaceutical dosage forms. The review represents the various analytical method like the RP-HPLC, HPTLC, UV Spectroscopy and Stability Indicating Methods which were used for the investigation of Venlafaxine in bulk and different dosage formulations.

Anxiolytic and Antidepressant-Like Effects of Conyza canadensis Aqueous Extract in the Scopolamine Rat Model

Conyza canadensis is a plant widely used in traditional medicine in Morocco for the treatment of varied health challenges. However, to the best of our knowledge, there is no scientific study justifying the traditional use of Conyza extract as an anxiolytic and antidepressant agent. Moreover, data regarding the polyphenolic fraction is limited. Therefore, the present study was conducted to investigate the chemical composition of an aqueous extract obtained from the aerial parts of Conyza, its antioxidant potential, and the anxiolytic and antidepressant-like effects of the sample (100 and 200 mg/kg body weight (bw)) in the scopolamine (Sco) (0.7 mg/kg bw) rat model. To achieve this purpose, a variety of antioxidant tests (including free radical-scavenging activity and lipoxygenase-inhibitory potential assays) and behavioral procedures, such as the elevated plus-maze and forced swimming tests, were performed. The results demonstrated that the aqueous extract of Conyza canadensis is rich in catechins and flavonoids which possess good antioxidant activity. Additionally, concentrations of 100 and 200 mg/kg of the extract exhibited significant anxiolytic and antidepressant-like profiles following scopolamine treatment. Therefore, we propose that the use of Conyza canadensis could be a new pharmacological target for the amelioration of major depression.

Serotonergic and noradrenergic response of ethanol extract; opioidergic response of ethyl acetate extract of Dicranopteris linearis L. leaf

Background Dicranopteris linearis L. is among the popular tribal plants used for various ailments, although many of its pharmacological potentials have not been investigated yet. The neuropharmacological potentials of the leaf, including sedative-anxiolytic potential, were previously studied however, the antidepressant activity was yet to be examined. Thus, this study was aimed to investigate the serotonergic, noradrenergic and opioidergic response of D. linearis leaf extracts. Methods The plant leaf was extracted in three solvents- water (DLAQ), ethanol (DLET) and ethyl acetate (DLEA) and applied each in 200 and 400 mg.kg− 1 per body weight of Swiss Albino mice. Forced Swim Test (FST) and Tail Suspension Test (TST) were conducted to evaluate antidepressant potential. In FST, latency and duration of immobility, swimming and climbing time were recorded. In TST, immobility, swinging, curling and pedaling were observed. Alongside, preliminary screening through acute toxicity study and pentobarbitone induced sleep test were performed. Results Both in FST and TST, the duration of immobility was reduced by the standard imipramine and DLET 200 and 400. In FST, DLEA 200 and 400 increased the climbing time suggesting noradrenergic mechanism of action and decreased the swimming time suggesting deficit of serotoninergic mechanism of action. Interestingly, DLET increased both the parameters presenting a dual action. However, in TST, DLEA decreased immobility but increased swinging and curling response which indicated its opioidergic mechanism. On the other hand, DLET proved to mediate through serotonin and/or NA reuptake mechanism by having decreased curling time. Conclusion Among the three extracts, the ethanol extract proved to be more potent. DLET mimicked the standard imipramine in all parameters except for the curling behavior. The result thus suggests D. linearis as a potent antidepressant agent however, recommends its medicinal use after further investigation to identify bioactive compounds.

Tetragonia tetragonioides Relieves Depressive-Like Behavior through the Restoration of Glial Loss in the Prefrontal Cortex

Tetragonia tetragonioides, which is a halophyte and grows widely in Asian-Pacific regions, has been used for the treatment of digestive disorders in traditional oriental medicine. This study examined the potential antidepressant effect of Tetragonia tetragonioides in an astroglial degeneration model of depression, which was established based on the postmortem study of depressive patients’ brain presenting diminished astrocytes in the prefrontal cortex. C57BL/6 male mice were exposed to glial ablation in the prefrontal cortex by the administration of the gliotoxin, L-alpha-aminoadipic acid (L-AAA) to induce depression. Tetragonia tetragonioides at doses of 100 mg/kg and 300 mg/kg, imipramine at a dose of 15 mg/kg, and distilled water were orally administrated to mice for 18 days. Behavioral tests including the open field test (OFT), sucrose preference test (SPT), forced swimming test (FST), and tail suspension test (TST) were carried out after 2 days of L-AAA injection. The expression levels of GFAP and NeuN in the prefrontal cortex were determined by immunohistochemistry. Mice subjected to glial ablation in the prefrontal cortex displayed decreased sucrose consumption in SPT and increased immobility time in FST and TST. Treatment with imipramine and Tetragonia tetragonioides remarkably ameliorated the behavioral despair induced by L-AAA. In addition, immunohistochemistry analysis showed that treatment with Tetragonia tetragonioides significantly restored the glial loss as indicated by the elevated GFAP expression level. These findings suggest that Tetragonia tetragonioides exerts an antidepressant effect through the restoration of glial loss under conditions of depression and can be a candidate for an antidepressant agent.

The potential anti-depressant properties of dexmedetomidine infusion: a review of mechanistic, preclinical, and clinical evidence

Major depressive disorder (MDD) is a highly prevalent and disabling condition for which the currently available treatments are not fully effective. Existing unmet needs include rapid onset of action and optimal management of concurrent agitation. Dexmedetomidine (DEX) is a selective and potent α2-adrenergic receptor (α2-AR) agonist, with unique pharmacokinetic and pharmacodynamic properties. In this review, we discuss pre-clinical and clinical studies which focused on DEX in the context of its putative antidepressant effects for the management of MDD. Preliminary data support DEX as an antidepressant with fast onset of action, which would be especially helpful for patients experiencing treatment resistant depression, and agitation. We further explore the mechanistic and clinical implications of considering DEX as a putative antidepressant agent, and the next steps to explore the efficacy of low dose DEX infusion among patients with treatment resistant depression.